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Trial record 16 of 25 for:    ASP 2215 OR Gilteritinib

Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of ASP2215 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT02014558
Recruitment Status : Completed
First Posted : December 18, 2013
Results First Posted : February 20, 2019
Last Update Posted : May 23, 2019
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Acute Myeloid Leukemia
Interventions Drug: Gilteritinib
Drug: Voriconazole
Drug: Midazolam
Drug: Cephalexin
Enrollment 265
Recruitment Details This dose-escalation/dose-expansion study was conducted in sites in the United States, France, Germany and Italy. The study had 7 dose-escalation cohorts with ≥3 participants enrolled at each dose level. Following escalation to the next dose cohort, additional participants were enrolled to the dose-expansion cohorts per protocol-specified criteria.
Pre-assignment Details Participants with acute myeloid leukemia (AML) who relapsed after or were refractory to induction or salvage treatment were selected for this study. Five participants were re-enrolled into the dose-expansion cohorts as they discontinued treatment for reasons other than toxicity or disease progression, as long as they met the eligibility criteria.
Arm/Group Title Gilteritinib 20 mg in Escalation Phase Gilteritinib 40 mg in Escalation Phase Gilteritinib 80 mg in Escalation Phase Gilteritinib 120 mg in Escalation Phase Gilteritinib 200 mg in Escalation Phase Gilteritinib 300 mg in Escalation Phase Gilteritinib 450 mg in Escalation Phase Gilteritinib 20 mg in Expansion Phase Gilteritinib 40 mg in Expansion Phase Gilteritinib 80 mg in Expansion Phase Gilteritinib 120 mg in Expansion Phase Gilteritinib 200 mg in Expansion Phase Gilteritinib 300 mg in Expansion Phase
Hide Arm/Group Description Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2. Participants received 40 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Participants received 80 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Participants received 120 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Participants received 200 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. Participants received 300 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Period Title: Overall Study
Started [1] 5 3 3 3 4 3 4 11 15 21 69 102 17
Treated 5 3 3 3 3 3 3 12 [2] 13 21 66 [2] 100 17
Completed 0 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 5 3 3 3 4 3 4 11 15 21 69 102 17
Reason Not Completed
Never Received Study Drug             0             0             0             0             1             0             1             0             2             0             2             2             0
Adverse Event             0             0             0             0             1             0             0             0             2             2             5             21             3
Death             1             0             0             0             0             0             1             1             2             5             5             19             2
Lack of Efficacy             1             2             1             1             0             0             1             3             3             3             16             8             5
Lost to Follow-up             0             0             0             0             0             0             0             0             0             0             1             0             0
Progressive Disease             1             0             1             1             1             2             1             6             5             6             22             31             6
Withdrawal by Subject             0             0             0             0             1             0             0             0             0             2             6             10             0
Miscellaneous             2             1             1             1             0             1             0             1             1             3             12             11             1
[1]
Re-enrolled participants (assigned to the 120 mg [1] & 200 mg [4] expansion groups) were excluded.
[2]
A participant randomized to the 120 mg was treated with an initial dose of 20 mg by mistake.
Arm/Group Title Gilteritinib 20 mg in Escalation Phase Gilteritinib 40 mg in Escalation Phase Gilteritinib 80 mg in Escalation Phase Gilteritinib 120 mg in Escalation Phase Gilteritinib 200 mg in Escalation Phase Gilteritinib 300 mg in Escalation Phase Gilteritinib 450 mg in Escalation Phase Gilteritinib 20 mg in Expansion Phase Gilteritinib 40 mg in Expansion Phase Gilteritinib 80 mg in Expansion Phase Gilteritinib 120 mg in Expansion Phase Gilteritinib 200 mg in Expansion Phase Gilteritinib 300 mg in Expansion Phase Total
Hide Arm/Group Description Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2. Participants received 40 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Participants received 80 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Participants received 120 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Participants received 200 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. Participants received 300 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. Total of all reporting groups
Overall Number of Baseline Participants 5 3 3 3 3 3 3 12 13 21 66 100 17 252
Hide Baseline Analysis Population Description
The analysis population was the safety analysis set (SAF), which consisted of all participants who received at least 1 dose of study drug and excluded re-enrolled participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants 3 participants 3 participants 3 participants 3 participants 3 participants 3 participants 12 participants 13 participants 21 participants 66 participants 100 participants 17 participants 252 participants
65.8  (6.8) 56.7  (6.7) 61  (8.7) 61.7  (6) 64  (1) 55.3  (25) 61.7  (10.7) 59.3  (15.6) 59.6  (14) 56.3  (18.1) 58.3  (16.7) 59.8  (14.6) 57.7  (15.9) 59  (15.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 3 participants 3 participants 3 participants 3 participants 3 participants 3 participants 12 participants 13 participants 21 participants 66 participants 100 participants 17 participants 252 participants
Female
2
  40.0%
1
  33.3%
1
  33.3%
1
  33.3%
2
  66.7%
1
  33.3%
0
   0.0%
8
  66.7%
4
  30.8%
12
  57.1%
37
  56.1%
49
  49.0%
5
  29.4%
123
  48.8%
Male
3
  60.0%
2
  66.7%
2
  66.7%
2
  66.7%
1
  33.3%
2
  66.7%
3
 100.0%
4
  33.3%
9
  69.2%
9
  42.9%
29
  43.9%
51
  51.0%
12
  70.6%
129
  51.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 3 participants 3 participants 3 participants 3 participants 3 participants 3 participants 12 participants 13 participants 21 participants 66 participants 100 participants 17 participants 252 participants
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
1
  33.3%
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
4
  19.0%
2
   3.0%
4
   4.0%
3
  17.6%
16
   6.3%
White
5
 100.0%
2
  66.7%
3
 100.0%
2
  66.7%
1
  33.3%
3
 100.0%
3
 100.0%
10
  83.3%
9
  69.2%
14
  66.7%
57
  86.4%
91
  91.0%
13
  76.5%
213
  84.5%
Asian
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.5%
4
   4.0%
0
   0.0%
7
   2.8%
Other
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
4
  30.8%
3
  14.3%
6
   9.1%
1
   1.0%
1
   5.9%
16
   6.3%
Ethnicity  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 3 participants 3 participants 3 participants 3 participants 3 participants 3 participants 12 participants 13 participants 21 participants 66 participants 100 participants 17 participants 252 participants
Not Hispanic or Latino
5
 100.0%
3
 100.0%
2
  66.7%
3
 100.0%
3
 100.0%
3
 100.0%
3
 100.0%
11
  91.7%
12
  92.3%
20
  95.2%
62
  93.9%
97
  97.0%
17
 100.0%
241
  95.6%
Hispanic or Latino
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
1
   7.7%
1
   4.8%
4
   6.1%
3
   3.0%
0
   0.0%
11
   4.4%
Duration of Disease (AML)   [1] 
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 4 participants 3 participants 2 participants 3 participants 2 participants 1 participants 3 participants 10 participants 11 participants 17 participants 46 participants 77 participants 15 participants 194 participants
19.70  (24.62) 10.81  (8.58) 62.46  (6.97) 49.53  (72.17) 9.46  (2.23) 19.75 [2]   (NA) 7.21  (4.27) 11.3  (6.61) 10.53  (11.22) 16.3  (9.85) 12.65  (11.33) 10.9  (9.94) 12.09  (17.76) 13.16  (14.97)
[1]
Measure Analysis Population Description: The analysis population was the SAF, with participants with data available.
[2]
Data could not be calculated as there is only one participant in this arm who had available data.
Local FLT3 Mutation Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 3 participants 3 participants 3 participants 3 participants 3 participants 3 participants 12 participants 13 participants 21 participants 66 participants 100 participants 17 participants 252 participants
Negative
1
  20.0%
0
   0.0%
0
   0.0%
1
  33.3%
1
  33.3%
1
  33.3%
1
  33.3%
1
   8.3%
8
  61.5%
12
  57.1%
13
  19.7%
10
  10.0%
9
  52.9%
58
  23.0%
Positive
4
  80.0%
3
 100.0%
3
 100.0%
2
  66.7%
2
  66.7%
2
  66.7%
2
  66.7%
11
  91.7%
5
  38.5%
9
  42.9%
53
  80.3%
90
  90.0%
8
  47.1%
194
  77.0%
1.Primary Outcome
Title Number of Participants With Dose Limiting Toxicities (DLTs)
Hide Description To determine the maximum tolerated dose, safety was assessed by DLTs, defined as any grade ≥ 3 non-hematologic or extramedullary toxicity that occurred within 30 days starting with the first dose taken on day -2, and included the first treatment cycle in the dose escalation phase and in the first treatment cycle (28 days) in the dose expansion phase, that was considered to be possibly or probably related to study drug. Exceptions to this were the following: (1) Alopecia, anorexia or fatigue, (2) Grade 3 nausea and/or vomiting if not required tube feeding or total parenteral nutrition, or diarrhea if not required or prolonged hospitalization that was managed to grade ≤ 2 with standard antiemetic or antidiarrheal medications used at prescribed dose within 7 days of onset, (3) Grade 3 fever with neutropenia, with or without infection, (4) Grade 3 infection.
Time Frame From first dose up to end of cycle 1 (30 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the SAF. Only evaluable participants (defined as participants who received at least 80% of the intended dose during cycle 1 [received at least 23 daily doses in escalation phase or 22 daily doses in expansion phase during cycle 1] or participants who developed DLT within cycle 1) were included.
Arm/Group Title Gilteritinib 20 mg in Escalation Phase Gilteritinib 40 mg in Escalation Phase Gilteritinib 80 mg in Escalation Phase Gilteritinib 120 mg in Escalation Phase Gilteritinib 200 mg in Escalation Phase Gilteritinib 300 mg in Escalation Phase Gilteritinib 450 mg in Escalation Phase Gilteritinib 20 mg in Expansion Phase Gilteritinib 40 mg in Expansion Phase Gilteritinib 80 mg in Expansion Phase Gilteritinib 120 mg in Expansion Phase Gilteritinib 200 mg in Expansion Phase Gilteritinib 300 mg in Expansion Phase
Hide Arm/Group Description:
Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2.
Participants received 40 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.
Participants received 80 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.
Participants received 120 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.
Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.
Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Overall Number of Participants Analyzed 3 3 3 3 3 3 3 9 11 18 62 87 13
Measure Type: Count of Participants
Unit of Measure: Participants
Any DLT
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  66.7%
1
  11.1%
1
   9.1%
2
  11.1%
7
  11.3%
15
  17.2%
3
  23.1%
Blood and lymphatic system disorders
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Cardiac disorders
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.6%
0
   0.0%
0
   0.0%
Eye disorders
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.6%
0
   0.0%
0
   0.0%
0
   0.0%
Gastrointestinal disorders
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.6%
4
   4.6%
1
   7.7%
General disorders & administration site conditions
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
0
   0.0%
Hepatobiliary disorders
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.6%
0
   0.0%
0
   0.0%
Infections and infestations
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   9.1%
1
   5.6%
0
   0.0%
0
   0.0%
0
   0.0%
Investigations
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
2
   3.2%
6
   6.9%
2
  15.4%
Metabolism and nutrition disorders
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.3%
0
   0.0%
Musculoskeletal and connective tissue disorders
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
1
   7.7%
Nervous system disorders
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
0
   0.0%
3
   3.4%
0
   0.0%
Renal and urinary disorders
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.6%
0
   0.0%
0
   0.0%
Reproductive system and breast disorders
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
0
   0.0%
Respiratory, thoracic and mediastinal disorders
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.6%
2
   2.3%
1
   7.7%
Vascular disorders
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.3%
1
   7.7%
2.Primary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A treatment-emergent AE (TEAE) was defined as an AE observed after starting administration of the study drug up to 30 days after last dose of study drug (for participants who underwent hematopoietic stem cell transplantation [HSCT]: defined as AEs observed after starting study drug until the last dose before on study HSCT plus 30 days, and AEs that began after resumption of gilteritinib and within 30 days after the last dose of gilteritinib). AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (1-Mild, 2-Moderate, 3-Severe, 4-LifeThreatening, 5-Death).
Time Frame From first dose of study drug up to 30 days after last dose of study drug (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the SAF.
Arm/Group Title Gilteritinib 20 mg in Escalation Phase Gilteritinib 40 mg in Escalation Phase Gilteritinib 80 mg in Escalation Phase Gilteritinib 120 mg in Escalation Phase Gilteritinib 200 mg in Escalation Phase Gilteritinib 300 mg in Escalation Phase Gilteritinib 450 mg in Escalation Phase Gilteritinib 20 mg in Expansion Phase Gilteritinib 40 mg in Expansion Phase Gilteritinib 80 mg in Expansion Phase Gilteritinib 120 mg in Expansion Phase Gilteritinib 200 mg in Expansion Phase Gilteritinib 300 mg in Expansion Phase
Hide Arm/Group Description:
Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2.
Participants received 40 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.
Participants received 80 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.
Participants received 120 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.
Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.
Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Overall Number of Participants Analyzed 5 3 3 3 3 3 3 12 13 21 66 100 17
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
5
 100.0%
3
 100.0%
3
 100.0%
3
 100.0%
3
 100.0%
3
 100.0%
3
 100.0%
12
 100.0%
13
 100.0%
20
  95.2%
64
  97.0%
100
 100.0%
17
 100.0%
Drug-Related AEs
3
  60.0%
2
  66.7%
1
  33.3%
3
 100.0%
3
 100.0%
2
  66.7%
3
 100.0%
7
  58.3%
6
  46.2%
17
  81.0%
52
  78.8%
77
  77.0%
13
  76.5%
Deaths
2
  40.0%
2
  66.7%
0
   0.0%
1
  33.3%
1
  33.3%
1
  33.3%
1
  33.3%
3
  25.0%
4
  30.8%
11
  52.4%
23
  34.8%
49
  49.0%
7
  41.2%
Serious AEs
2
  40.0%
2
  66.7%
2
  66.7%
1
  33.3%
2
  66.7%
2
  66.7%
2
  66.7%
8
  66.7%
12
  92.3%
19
  90.5%
52
  78.8%
92
  92.0%
14
  82.4%
Drug-Related Serious AEs
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
1
  33.3%
0
   0.0%
2
  66.7%
2
  16.7%
1
   7.7%
10
  47.6%
19
  28.8%
36
  36.0%
4
  23.5%
AEs Leading to Discontinuation of Study Drug
2
  40.0%
0
   0.0%
1
  33.3%
0
   0.0%
1
  33.3%
0
   0.0%
1
  33.3%
2
  16.7%
5
  38.5%
11
  52.4%
12
  18.2%
46
  46.0%
6
  35.3%
Drug-Related AEs Leading to Discont. of Study Drug
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
1
   7.7%
4
  19.0%
5
   7.6%
10
  10.0%
3
  17.6%
Grade 3 or Higher TEAEs
3
  60.0%
2
  66.7%
2
  66.7%
1
  33.3%
2
  66.7%
2
  66.7%
3
 100.0%
9
  75.0%
13
 100.0%
20
  95.2%
59
  89.4%
99
  99.0%
14
  82.4%
AEs During On-Study HSCT Period
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
   4.5%
7
   7.0%
0
   0.0%
Serious AEs During On-Study HSCT
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
   3.0%
0
   0.0%
3.Primary Outcome
Title Area Under the Concentration-time Curve Over the 24-Hour Dosing Interval (AUC24) After Single and Multiple Doses of Gilteritinib
Hide Description Plasma samples were used for pharmacokinetic assessments.
Time Frame Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics analysis set (PKAS) - consisted of the subset of the SAF for which sufficient plasma concentration data were available to facilitate derivation of at least 1 pharmacokinetic parameter and for whom the time of dosing on the day of sampling was known. Participants with available data were included in the analysis.
Arm/Group Title Gilteritinib 20 mg in Escalation Phase Gilteritinib 40 mg in Escalation Phase Gilteritinib 80 mg in Escalation Phase Gilteritinib 120 mg in Escalation Phase Gilteritinib 200 mg in Escalation Phase Gilteritinib 300 mg in Escalation Phase Gilteritinib 450 mg in Escalation Phase
Hide Arm/Group Description:
Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Overall Number of Participants Analyzed 5 3 3 3 3 3 3
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
Day -2 Number Analyzed 5 participants 3 participants 3 participants 3 participants 3 participants 3 participants 2 participants
302.1  (207.0) 360.0  (223.5) 1216  (472.6) 2480  (1972) 3022  (843.6) 4163  (3178) 3324  (221.1)
Cycle 1 Day 15 Number Analyzed 3 participants 2 participants 3 participants 3 participants 2 participants 3 participants 1 participants
1299  (1006) 2482  (33.28) 6958  (3273) 6943  (3221) 31428  (21412) 31005  (10068) 34768 [1]   (NA)
[1]
This cannot be calculated due to insufficient data (only 1 participant had available data).
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilteritinib 20 mg in Escalation Phase, Gilteritinib 40 mg in Escalation Phase, Gilteritinib 80 mg in Escalation Phase, Gilteritinib 120 mg in Escalation Phase, Gilteritinib 200 mg in Escalation Phase, Gilteritinib 300 mg in Escalation Phase, Gilteritinib 450 mg in Escalation Phase
Comments Dose Proportionality (Single Dose / Day -2) was evaluated using the power model.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.990
Confidence Interval (2-Sided) 90%
0.788 to 1.19
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Gilteritinib 20 mg in Escalation Phase, Gilteritinib 40 mg in Escalation Phase, Gilteritinib 80 mg in Escalation Phase, Gilteritinib 120 mg in Escalation Phase, Gilteritinib 200 mg in Escalation Phase, Gilteritinib 300 mg in Escalation Phase, Gilteritinib 450 mg in Escalation Phase
Comments Dose Proportionality (Multiple Dose / Cycle 1 Day 15) was evaluated using the power model.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.22
Confidence Interval (2-Sided) 90%
1.00 to 1.43
Estimation Comments [Not Specified]
4.Primary Outcome
Title Maximum Concentration (Cmax) After Single and Multiple Doses of Gilteritinib
Hide Description Plasma samples were used for pharmacokinetic assessments.
Time Frame Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the PKAS with available data.
Arm/Group Title Gilteritinib 20 mg in Escalation Phase Gilteritinib 40 mg in Escalation Phase Gilteritinib 80 mg in Escalation Phase Gilteritinib 120 mg in Escalation Phase Gilteritinib 200 mg in Escalation Phase Gilteritinib 300 mg in Escalation Phase Gilteritinib 450 mg in Escalation Phase
Hide Arm/Group Description:
Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study..
Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study..
Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Overall Number of Participants Analyzed 5 3 3 3 3 3 3
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day -2 Number Analyzed 5 participants 3 participants 3 participants 3 participants 3 participants 3 participants 3 participants
28.13  (21.49) 24.98  (14.58) 75.29  (25.22) 136.7  (94.37) 168.2  (45.34) 204.3  (136.4) 207.6  (51.81)
Cycle 1 day 15 Number Analyzed 4 participants 3 participants 3 participants 3 participants 2 participants 3 participants 1 participants
64.64  (48.77) 107.6  (31.92) 376.4  (150.5) 374.2  (190.1) 1462  (815.1) 1525  (664.6) 1528 [1]   (NA)
[1]
This cannot be calculated due to insufficient data (only 1 participant had available data).
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilteritinib 20 mg in Escalation Phase, Gilteritinib 40 mg in Escalation Phase, Gilteritinib 80 mg in Escalation Phase, Gilteritinib 120 mg in Escalation Phase, Gilteritinib 200 mg in Escalation Phase, Gilteritinib 300 mg in Escalation Phase, Gilteritinib 450 mg in Escalation Phase
Comments Dose Proportionality (Single Dose / Day -2) was evaluated using the power model.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.808
Confidence Interval (2-Sided) 90%
0.629 to 0.988
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Gilteritinib 20 mg in Escalation Phase, Gilteritinib 40 mg in Escalation Phase, Gilteritinib 80 mg in Escalation Phase, Gilteritinib 120 mg in Escalation Phase, Gilteritinib 200 mg in Escalation Phase, Gilteritinib 300 mg in Escalation Phase, Gilteritinib 450 mg in Escalation Phase
Comments Dose Proportionality (Multiple Dose / Cycle 1 Day 15) was evaluated using the power model.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.21
Confidence Interval (2-Sided) 90%
1.02 to 1.41
Estimation Comments [Not Specified]
5.Primary Outcome
Title Area Under the Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) After Single and Multiple Doses of Gilteritinib
Hide Description Plasma samples were used for pharmacokinetic assessments.
Time Frame Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the PKAS with available data.
Arm/Group Title Gilteritinib 20 mg in Escalation Phase Gilteritinib 40 mg in Escalation Phase Gilteritinib 80 mg in Escalation Phase Gilteritinib 120 mg in Escalation Phase Gilteritinib 200 mg in Escalation Phase Gilteritinib 300 mg in Escalation Phase Gilteritinib 450 mg in Escalation Phase
Hide Arm/Group Description:
Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Overall Number of Participants Analyzed 5 3 3 3 3 3 3
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
Day -2 Number Analyzed 5 participants 3 participants 3 participants 3 participants 3 participants 3 participants 3 participants
303.0  (207.1) 360.4  (224.1) 1216  (472.6) 2480  (1972) 3024  (846.2) 4181  (3189) 2544  (1427)
Cycle 1 day -15 Number Analyzed 4 participants 3 participants 3 participants 3 participants 2 participants 3 participants 1 participants
1030  (984.2) 1990  (1422) 7111  (3525) 6943  (3221) 32248  (22571) 31749  (10090) 35506 [1]   (NA)
[1]
This cannot be calculated due to insufficient data (only 1 participant had available data).
6.Primary Outcome
Title Time to Observed Cmax (Tmax) After Single and Multiple Doses of Gilteritinib
Hide Description Plasma samples were used for pharmacokinetic assessments.
Time Frame Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the PKAS with available data.
Arm/Group Title Gilteritinib 20 mg in Escalation Phase Gilteritinib 40 mg in Escalation Phase Gilteritinib 80 mg in Escalation Phase Gilteritinib 120 mg in Escalation Phase Gilteritinib 200 mg in Escalation Phase Gilteritinib 300 mg in Escalation Phase Gilteritinib 450 mg in Escalation Phase
Hide Arm/Group Description:
Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Overall Number of Participants Analyzed 5 3 3 3 3 3 3
Median (Full Range)
Unit of Measure: hours
Day -2 Number Analyzed 5 participants 3 participants 3 participants 3 participants 3 participants 3 participants 3 participants
2.00
(0.500 to 4.03)
5.983
(3.97 to 24.0)
4.000
(4.00 to 4.08)
2.083
(2.00 to 3.83)
5.233
(4.00 to 5.97)
6.067
(4.08 to 24.1)
5.783
(4.08 to 5.92)
Cycle 1 day 15 Number Analyzed 4 participants 3 participants 3 participants 3 participants 2 participants 3 participants 1 participants
4.008
(4.00 to 6.00)
3.867
(0.50 to 6.00)
4.333
(4.00 to 4.42)
2.167
(1.95 to 5.75)
6.033
(6.00 to 6.07)
6.050
(4.08 to 6.07)
5.933 [1] 
(NA to NA)
[1]
This cannot be calculated due to insufficient data (only 1 participant had available data).
7.Primary Outcome
Title Terminal Elimination Half-life (t1/2) After Multiple Doses of Gilteritinib
Hide Description Plasma samples were used for pharmacokinetic assessments.
Time Frame Cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the PKAS with available data.
Arm/Group Title Gilteritinib 20 mg in Escalation Phase Gilteritinib 40 mg in Escalation Phase Gilteritinib 80 mg in Escalation Phase Gilteritinib 120 mg in Escalation Phase Gilteritinib 200 mg in Escalation Phase Gilteritinib 300 mg in Escalation Phase Gilteritinib 450 mg in Escalation Phase
Hide Arm/Group Description:
Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Overall Number of Participants Analyzed 3 2 3 3 2 3 0
Mean (Standard Deviation)
Unit of Measure: hours
62.14  (17.88) 151.8  (129.2) 86.11  (24.08) 45.85  (18.83) 141.9  (61.51) 142.2  (55.04)
8.Primary Outcome
Title Accumulation Ratio After Multiple Doses of Gilteritinib
Hide Description Plasma samples were used for pharmacokinetic assessments.
Time Frame Cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the PKAS with available data.
Arm/Group Title Gilteritinib 20 mg in Escalation Phase Gilteritinib 40 mg in Escalation Phase Gilteritinib 80 mg in Escalation Phase Gilteritinib 120 mg in Escalation Phase Gilteritinib 200 mg in Escalation Phase Gilteritinib 300 mg in Escalation Phase Gilteritinib 450 mg in Escalation Phase
Hide Arm/Group Description:
Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in in the escalation phase of the study.28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Overall Number of Participants Analyzed 3 2 3 3 2 3 0
Mean (Standard Deviation)
Unit of Measure: ratio
4.259  (1.069) 9.640  (7.754) 5.693  (1.442) 3.290  (1.118) 9.041  (3.693) 9.057  (3.303)
9.Secondary Outcome
Title Percentage of Participants With Complete Remission (CR) During the First 2 Cycles
Hide Description CR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CR when they had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an absolute neutrophil count (ANC) > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, normal marrow differential with < 5% blasts, had been red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion), had no presence of Auer rods and no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Exact 95% confidence interval was estimated using binomial distribution.
Time Frame During the first 2 cycles (56 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) - consisted of all participants who were enrolled, took at least 1 dose of study drug and who had at least 1 posttreatment data point. Re-enrolled participants and participants from one site due to concerns with this site’s GCP compliance were excluded. Participants were summarized under planned reporting groups in the FAS.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 16 16 24 70 100 20 3
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
FLT3 Mutation Positive Number Analyzed 14 participants 8 participants 12 participants 56 participants 89 participants 10 participants 2 participants
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
8.3
(0.2 to 38.5)
3.6
(0.4 to 12.3)
3.4
(0.7 to 9.5)
10
(0.3 to 44.5)
0 [1] 
(NA to NA)
FLT3 Mutation Negative Number Analyzed 2 participants 8 participants 12 participants 14 participants 11 participants 10 participants 1 participants
50.0
(1.3 to 98.7)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
All Participants Number Analyzed 16 participants 16 participants 24 participants 70 participants 100 participants 20 participants 3 participants
6.3
(0.2 to 30.2)
0 [1] 
(NA to NA)
4.2
(0.1 to 21.1)
2.9
(0.3 to 9.9)
3.0
(0.6 to 8.5)
5.0
(0.1 to 24.9)
0 [1] 
(NA to NA)
[1]
Data could not be calculated due to the low number of events.
10.Secondary Outcome
Title Percentage of Participants With CR During Treatment
Hide Description CR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CR when they had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an absolute neutrophil count (ANC) > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, normal marrow differential with < 5% blasts, had been red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion), had no presence of Auer rods and no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Exact 95% confidence interval was estimated using binomial distribution.
Time Frame Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 16 16 24 70 100 20 3
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
FLT3 Mutation Positive Number Analyzed 14 participants 8 participants 12 participants 56 participants 89 participants 10 participants 2 participants
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
16.7
(2.1 to 48.4)
12.5
(5.2 to 24.1)
11.2
(5.5 to 19.7)
10.0
(0.3 to 44.5)
0 [1] 
(NA to NA)
FLT3 Mutation Negative Number Analyzed 2 participants 8 participants 12 participants 14 participants 11 participants 10 participants 1 participants
50.0
(1.3 to 98.7)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
All Participants Number Analyzed 16 participants 16 participants 24 participants 70 participants 100 participants 20 participants 3 participants
6.3
(0.2 to 30.2)
0 [1] 
(NA to NA)
8.3
(1.0 to 27.0)
10.0
(4.1 to 19.5)
10.0
(4.9 to 17.6)
5.0
(0.1 to 54.9)
0 [1] 
(NA to NA)
[1]
Data could not be calculated due to the low number of events.
11.Secondary Outcome
Title Percentage of Participants With CR With Incomplete Platelet Recovery (CRp)
Hide Description CRp was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRp when they achieved CR except for incomplete platelet recovery (< 100 x 10^9/L). Exact 95% confidence interval was estimated using the binomial distribution.
Time Frame Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 16 16 24 70 100 20 3
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
FLT3 Mutation Positive Number Analyzed 14 participants 8 participants 12 participants 56 participants 89 participants 10 participants 2 participants
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
3.6
(0.4 to 12.3)
9.0
(4.0 to 16.9)
10.0
(0.3 to 44.5)
0 [1] 
(NA to NA)
FLT3 Mutation Negative Number Analyzed 2 participants 8 participants 12 participants 14 participants 11 participants 10 participants 1 participants
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
All Participants Number Analyzed 16 participants 16 participants 24 participants 70 participants 100 participants 20 participants 3 participants
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
2.9
(0.3 to 9.9)
8.0
(3.5 to 15.2)
5.0
(0.1 to 24.9)
0 [1] 
(NA to NA)
[1]
Data could not be calculated due to the low number of events.
12.Secondary Outcome
Title Percentage of Participants With CR With Incomplete Hematological Recovery (CRi)
Hide Description CRi was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRi when they fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery. RBC and platelet transfusion independence were not required. Exact 95% confidence interval was estimated using the binomial distribution.
Time Frame Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 16 16 24 70 100 20 3
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
FLT3 Mutation Positive Number Analyzed 14 participants 8 participants 12 participants 56 participants 89 participants 10 participants 2 participants
7.1
(0.2 to 33.9)
0 [1] 
(NA to NA)
25.0
(5.5 to 57.2)
30.4
(18.8 to 44.1)
20.2
(12.4 to 30.1)
10.0
(0.3 to 44.5)
0 [1] 
(NA to NA)
FLT3 Mutation Negative Number Analyzed 2 participants 8 participants 12 participants 14 participants 11 participants 10 participants 1 participants
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
16.7
(2.1 to 48.4)
7.1
(0.2 to 33.9)
9.1
(0.2 to 41.3)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
All Participants Number Analyzed 16 participants 16 participants 24 participants 70 participants 100 participants 20 participants 3 participants
6.3
(0.2 to 30.2)
0 [1] 
(NA to NA)
20.8
(7.1 to 42.2)
25.7
(16.0 to 37.6)
19.0
(11.8 to 28.1)
5.0
(0.1 to 24.9)
0 [1] 
(NA to NA)
[1]
Data could not be calculated due to the low number of events.
13.Secondary Outcome
Title Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh)
Hide Description CRh was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRh when they could not be classified as being in CR and had bone marrow blasts < 5% and partial hematologic recovery ANC >= 0.5 x 10^9/L and platelets >= 50 x 10^9/L. There should not be evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution. CRh was calculated only for participants who were FLT3 mutation positive.
Time Frame Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS, with participants who were FLT3 mutation positive.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 14 8 12 56 89 10 2
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
7.1
(0.2 to 33.9)
0
(0 to 0)
8.3
(0.2 to 38.5)
10.7
(4.0 to 21.9)
7.9
(3.2 to 15.5)
20.0
(2.5 to 55.6)
0
(0 to 0)
14.Secondary Outcome
Title Percentage of Participants With Composite CR (CRc)
Hide Description CRc was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRc when they had achieved either CR, complete remission with incomplete platelet recovery (CRp, defined as had achieved CR except for incomplete platelet recovery (< 100 x 10^9/L) or complete remission with incomplete hematologic recovery (CRi, defined as had fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery; RBC platelet transfusion independence not required). Exact 95% confidence interval was estimated using the binomial distribution.
Time Frame Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 16 16 24 70 100 20 3
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
FLT3 Mutation Positive Number Analyzed 14 participants 8 participants 12 participants 56 participants 89 participants 10 participants 2 participants
7.1
(0.2 to 33.9)
0 [1] 
(NA to NA)
41.7
(15.2 to 72.3)
46.4
(33.0 to 60.3)
40.4
(30.2 to 51.4)
30.0
(6.7 to 65.2)
0 [1] 
(NA to NA)
FLT3 Mutation Negative Number Analyzed 2 participants 8 participants 12 participants 14 participants 11 participants 10 participants 1 participants
50.0
(1.3 to 98.7)
0 [1] 
(NA to NA)
16.7
(2.1 to 48.4)
7.1
(0.2 to 33.9)
9.1
(0.2 to 41.3)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
All Participants Number Analyzed 16 participants 16 participants 24 participants 70 participants 100 participants 20 participants 3 participants
12.5
(1.6 to 38.3)
0 [1] 
(NA to NA)
29.2
(12.6 to 51.1)
38.6
(27.2 to 51.0)
37.0
(27.6 to 47.2)
15.0
(3.2 to 37.9)
0 [1] 
(NA to NA)
[1]
Data could not be calculated due to the low number of events.
15.Secondary Outcome
Title Percentage of Participants With Partial Remission (PR)
Hide Description PR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in PR when they had bone marrow regenerating normal hematopoietic cells with evidence of peripheral recovery with no (or only a few regenerating) circulating blasts and with a decrease of at least 50% in the percentage of blasts in the bone marrow aspirate with the total marrow blasts between 5% and 25%. A value of less or equal than 5% blasts was also considered a PR if Auer rods were present. There should be no evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution.
Time Frame Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 16 16 24 70 100 20 3
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
FLT3 Mutation Positive Number Analyzed 14 participants 8 participants 12 participants 56 participants 89 participants 10 participants 2 participants
7.1
(0.2 to 33.9)
37.5
(8.5 to 75.5)
25.0
(5.5 to 57.2)
7.1
(2.0 to 17.3)
7.9
(3.2 to 15.5)
30.0
(6.7 to 65.2)
50.0
(1.3 to 98.7)
FLT3 Mutation Negative Number Analyzed 2 participants 8 participants 12 participants 14 participants 11 participants 10 participants 1 participants
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
7.1
(0.2 to 33.9)
9.1
(0.2 to 41.3)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
All Participants Number Analyzed 16 participants 16 participants 24 participants 70 participants 100 participants 20 participants 3 participants
6.3
(0.2 to 30.2)
18.8
(4.0 to 45.6)
12.5
(2.7 to 32.4)
7.1
(2.4 to 15.9)
8.0
(3.5 to 15.2)
15.0
(3.2 to 37.9)
33.3
(0.8 to 90.6)
[1]
Data could not be calculated due to the low number of events.
16.Secondary Outcome
Title Percentage of Participants With Best Response
Hide Description Best response was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). BR was defined as the best measured response for all visits (in the order of CR, CRp, CRi, and PR) post-treatment. Participants who achieved the best response of CR, CRp, CRi or PR were classified as responders. Participants who did not achieve at least PR were considered as non-responders. Exact 95% confidence interval was estimated using the binomial distribution.
Time Frame Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 16 16 24 70 100 20 3
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
FLT3 Mutation Positive Number Analyzed 14 participants 8 participants 12 participants 56 participants 89 participants 10 participants 2 participants
14.3
(1.8 to 42.8)
37.5
(8.5 to 75.5)
66.7
(34.9 to 90.1)
53.6
(39.7 to 67.0)
48.3
(37.6 to 59.2)
60.0
(26.2 to 87.8)
50.0
(1.3 to 98.7)
FLT3 Mutation Negative Number Analyzed 2 participants 8 participants 12 participants 14 participants 11 participants 10 participants 1 participants
50.0
(1.3 to 98.7)
0 [1] 
(NA to NA)
16.7
(2.1 to 48.4)
14.3
(1.8 to 42.8)
18.2
(2.3 to 51.8)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
All Participants Number Analyzed 16 participants 16 participants 24 participants 70 participants 100 participants 20 participants 3 participants
18.8
(4.0 to 45.6)
18.8
(4.0 to 45.6)
41.7
(22.1 to 63.4)
45.7
(33.7 to 58.1)
45.0
(35.0 to 55.3)
30.0
(11.9 to 54.3)
33.3
(0.8 to 90.6)
[1]
Data could not be calculated due to the low number of events.
17.Secondary Outcome
Title Percentage of Participants With Complete Remission and Complete Remission With Partial Hematologic Recovery (CR/CRh)
Hide Description Participants with CR/CRh were defined as participants who achieved either CR or CRh. Participants with CR had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an ANC > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, and normal marrow differential with < 5% blasts, had been RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). Also, there had been no presence of Auer rods, no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Participants with CRh could not be classified as being in CR and had bone marrow blasts < 5%, partial hematologic recovery ANC >= 0.5 x 10^9/L and platelets >= 50 x 10^9/L. There should not be evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution. CR/CRh was calculated only for participants who were FLT3 mutation positive.
Time Frame Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS, with participants who were FLT3 mutation positive.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 14 8 12 56 89 10 2
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
7.1
(0.2 to 33.9)
0 [1] 
(NA to NA)
25.0
(5.5 to 57.2)
23.2
(13.0 to 36.4)
19.1
(11.5 to 28.8)
30.0
(6.7 to 65.2)
0 [1] 
(NA to NA)
[1]
Data could not be calculated due to the low number of events.
18.Secondary Outcome
Title Duration of CR (DCR)
Hide Description DCR was defined as the time from the date of first CR until the date of documented relapse for participants who achieved CR. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study were considered non-events and censored at the last relapse-free disease assessment date. DCR was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CR were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 1 0 2 7 10 1 0
Median (95% Confidence Interval)
Unit of Measure: days
FLT3 Mutation Positive Number Analyzed 0 participants 0 participants 2 participants 7 participants 10 participants 1 participants 0 participants
NA [1] 
(NA to NA)
NA [1] 
(86.0 to NA)
419.0 [1] 
(64.0 to NA)
NA [1] 
(NA to NA)
FLT3 Mutation Negative Number Analyzed 1 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants
NA [1] 
(NA to NA)
All Participants Number Analyzed 1 participants 0 participants 2 participants 7 participants 10 participants 1 participants 0 participants
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(86.0 to NA)
419.0 [1] 
(64.0 to NA)
NA [1] 
(NA to NA)
[1]
Data could not be calculated due to the low number of events.
19.Secondary Outcome
Title Duration of CRp (DCRp)
Hide Description DCRp was defined as the time from the date of first CRp until the date of documented relapse for participants who achieved CRp. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study were considered non-events and censored at the last relapse-free disease assessment date. DCRp was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CRp were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 0 0 1 6 12 2 0
Median (95% Confidence Interval)
Unit of Measure: days
FLT3 Mutation Positive Number Analyzed 0 participants 0 participants 1 participants 6 participants 12 participants 2 participants 0 participants
NA [1] 
(NA to NA)
NA [1] 
(57.0 to NA)
450.0 [1] 
(43.0 to NA)
NA [1] 
(NA to NA)
FLT3 Mutation Negative Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants
All Participants Number Analyzed 0 participants 0 participants 1 participants 6 participants 12 participants 2 participants 0 participants
NA [1] 
(NA to NA)
NA [1] 
(57.0 to NA)
450.0 [1] 
(43.0 to NA)
NA [1] 
(NA to NA)
[1]
Data could not be calculated due to the low number of events.
20.Secondary Outcome
Title Duration of CRi (DCRi)
Hide Description DCRi was defined as the time from the date of first CRi until the date of documented relapse for participants who achieved CRi. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRi was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CRi were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 1 0 7 24 31 1 0
Median (95% Confidence Interval)
Unit of Measure: days
FLT3 Mutation Positive Number Analyzed 1 participants 0 participants 5 participants 23 participants 30 participants 1 participants 0 participants
NA [1] 
(NA to NA)
NA [1] 
(79.0 to NA)
120.0
(56.0 to 383.0)
191.0
(57.0 to 420.0)
NA [1] 
(NA to NA)
FLT3 Mutation Negative Number Analyzed 0 participants 0 participants 2 participants 1 participants 0 participants 0 participants 0 participants
41.0
(22.0 to 60.0)
99.0 [1] 
(NA to NA)
All Participants Number Analyzed 1 participants 0 participants 7 participants 24 participants 31 participants 1 participants 0 participants
NA [1] 
(NA to NA)
79.0 [1] 
(22.0 to NA)
120.0
(58.0 to 383.0)
191.0
(57.0 to 420.0)
NA [1] 
(NA to NA)
[1]
Data could not be calculated due to the low number of events.
21.Secondary Outcome
Title Duration of CRh (DCRh)
Hide Description DCRh was defined as the time from the date of first CRh until the date of documented relapse for participants who achieved CRh but did not have a best response of CR. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRh was calculated using Kaplan-Meier method and therefore data are estimated. DCRh was calculated only for participants who were FLT3 mutation positive.
Time Frame From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CRh were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 1 0 1 6 7 2 0
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
64.0
(18.0 to 85.0)
101.0 [1] 
(29.0 to NA)
NA [1] 
(NA to NA)
[1]
Data could not be calculated due to the low number of events.
22.Secondary Outcome
Title Duration of CRc (DCRc)
Hide Description DCRc was defined as the time from the date of first CRc until the date of documented relapse for participants who achieved CRc. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRc was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CRc were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 2 0 7 27 37 3 0
Median (95% Confidence Interval)
Unit of Measure: days
FLT3 Mutation Positive Number Analyzed 1 participants 0 participants 5 participants 26 participants 36 participants 3 participants 0 participants
NA [1] 
(NA to NA)
NA [1] 
(79.0 to NA)
98.0
(57.0 to 307.0)
191.0
(101.0 to 465.0)
NA [1] 
(NA to NA)
FLT3 Mutation Negative Number Analyzed 1 participants 0 participants 2 participants 1 participants 1 participants 0 participants 0 participants
NA [1] 
(NA to NA)
41.0
(22.0 to 60.0)
99.0 [1] 
(NA to NA)
NA [1] 
(NA to NA)
All Participants Number Analyzed 2 participants 0 participants 7 participants 27 participants 37 participants 3 participants 0 participants
NA [1] 
(NA to NA)
79.0 [1] 
(22.0 to NA)
99.0
(58.0 to 307.0)
191.0
(101.0 to 465.0)
NA [1] 
(NA to NA)
[1]
Data could not be calculated due to the low number of events.
23.Secondary Outcome
Title Duration of CR/CRh (DCRCRh)
Hide Description DCRCRh was defined as the time from the date of first DCRCRh until the date of documented relapse for participants who achieved CR or CRh. For participants who achieved both CR and CRh, the first CR date or CRh date, whichever occurred first, was used. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRCRh was calculated using Kaplan-Meier method and therefore data are estimated. DCRCRh was calculated only for participants who were FLT3 mutation positive.
Time Frame From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CR or CRh were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 1 0 3 13 17 3 0
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
307.0 [1] 
(56.0 to NA)
308.0 [1] 
(101.0 to NA)
NA [1] 
(NA to NA)
[1]
Data could not be calculated due to the low number of events.
24.Secondary Outcome
Title Duration of Response
Hide Description Duration of response was defined as the time from the date of either first CRc or PR until the date of documented relapse of any type for participants who achieved CRc or PR. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study are considered non-events and censored at the last relapse-free assessment date. Duration of response was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CRc or PR were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 3 3 10 32 45 6 1
Median (95% Confidence Interval)
Unit of Measure: days
FLT3 Mutation Positive Number Analyzed 2 participants 3 participants 8 participants 30 participants 43 participants 6 participants 1 participants
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
88.0 [1] 
(9.0 to NA)
141.0
(58.0 to 383.0)
220.0
(111.0 to 482.0)
59.0
(15.0 to 59.0)
NA [1] 
(NA to NA)
FLT3 Mutation Negative Number Analyzed 1 participants 0 participants 2 participants 2 participants 2 participants 0 participants 0 participants
NA [1] 
(NA to NA)
41.0
(22.0 to 60.0)
109.5
(99.0 to 120.0)
85.0 [1] 
(NA to NA)
All Participants Number Analyzed 3 participants 3 participants 10 participants 32 participants 45 participants 6 participants 1 participants
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
79.0 [1] 
(9.0 to NA)
126.0
(58.0 to 307.0)
220.0
(85.0 to 482.0)
59.0
(15.0 to 59.0)
NA [1] 
(NA to NA)
[1]
Data could not be calculated due to the low number of events.
25.Secondary Outcome
Title Time to CR (TTCR)
Hide Description TTCR was defined as the time from the first dose of study drug until the date of first CR.
Time Frame From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CR were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 1 0 2 7 10 1 0
Median (Full Range)
Unit of Measure: days
FLT3 Mutation Positive Number Analyzed 0 participants 0 participants 2 participants 7 participants 10 participants 1 participants 0 participants
171.5
(28 to 315)
141.0
(29 to 364)
93.0
(27 to 225)
56.0
(56 to 56)
FLT3 Mutation Negative Number Analyzed 1 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants
30.0
(30 to 30)
All Participants Number Analyzed 1 participants 0 participants 2 participants 7 participants 10 participants 1 participants 0 participants
30.0
(30 to 30)
171.5
(28 to 315)
141.0
(29 to 364)
93.0
(27 to 225)
56.0
(56 to 56)
26.Secondary Outcome
Title Time to CRp (TTCRp)
Hide Description TTCRp was defined as the time from the first dose of study drug until the date of first CRp. TTCRp was evaluated for participants who achieved CRp.
Time Frame From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CRp were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 0 0 1 6 12 2 0
Median (Full Range)
Unit of Measure: days
FLT3 Mutation Positive Number Analyzed 0 participants 0 participants 1 participants 6 participants 12 participants 2 participants 0 participants
140.0
(140 to 140)
195.0
(30 to 418)
84.5
(28 to 392)
29.0
(28 to 30)
FLT3 Mutation Negative Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants
All Participants Number Analyzed 0 participants 0 participants 1 participants 6 participants 12 participants 2 participants 0 participants
140.0
(140 to 140)
195.0
(30 to 418)
84.5
(28 to 392)
29.0
(28 to 30)
27.Secondary Outcome
Title Time to CRi (TTCRi)
Hide Description TTCRi was defined as the time from the first dose of study drug until the date of first CRi. TTCRi was evaluated for participants who achieved CRi.
Time Frame From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CRi were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 1 0 7 24 31 1 0
Median (Full Range)
Unit of Measure: days
FLT3 Mutation Positive Number Analyzed 1 participants 0 participants 5 participants 23 participants 30 participants 1 participants 0 participants
57.0
(57 to 57)
57.0
(31 to 70)
57.0
(26 to 170)
39.5
(26 to 133)
28.0
(28 to 28)
FLT3 Mutation Negative Number Analyzed 0 participants 0 participants 2 participants 1 participants 1 participants 0 participants 0 participants
71.5
(71 to 72)
30.0
(30 to 30)
30.0
(30 to 30)
All Participants Number Analyzed 1 participants 0 participants 7 participants 24 participants 31 participants 1 participants 0 participants
57.0
(57 to 57)
64.0
(31 to 72)
43.5
(26 to 170)
35.0
(26 to 133)
28.0
(28 to 28)
28.Secondary Outcome
Title Time to First CR/CRh (TTFCRCRh)
Hide Description TTFCRCRh was defined as the time from the first dose of study drug until the date of first either CR or CRh. TTFCRCRh was evaluated for participants who achieved CR or CRh. For participants who achieve both CR and CRh, the first CR date or CRh date, whichever occurs first was used. TTFCRCRh was calculated only for participants who were FLT3 mutation positive.
Time Frame From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CR or CRh were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 1 0 3 13 17 3 0
Median (Full Range)
Unit of Measure: days
57.0
(57 to 57)
57.0
(28 to 140)
59.0
(29 to 280)
57.0
(27 to 245)
28.0
(28 to 30)
29.Secondary Outcome
Title Time to Best CR/CRh (TTBCRCRh)
Hide Description TTBCRCRh was defined as the time from the first dose of study drug until the first date that the best response of CR or CRh was achieved. TTBCRCRh was evaluated for participants who achieved CR or CRh. For participants who achieve both CR and CRh, the first CR date was used. TTBCRCRh was calculated only for participants who were FLT3 mutation positive.
Time Frame From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Participants who achieved CR or CRh were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 1 0 3 13 17 3 0
Median (Full Range)
Unit of Measure: days
57.0
(57 to 57)
57.0
(28 to 315)
63.0
(29 to 364)
88.0
(27 to 245)
30.0
(28 to 56)
30.Secondary Outcome
Title Time to CRc (TTCRc)
Hide Description TTCRc was defined as the time from the first dose of study drug until the date of first CRc. TTCRc was evaluated for participants who achieved CRc.
Time Frame From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CRc were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 2 0 7 27 37 3 0
Median (Full Range)
Unit of Measure: days
FLT3 Mutation Positive Number Analyzed 1 participants 0 participants 5 participants 26 participants 36 participants 3 participants 0 participants
57.0
(57 to 57)
56.0
(28 to 64)
30.0
(26 to 211)
31.5
(26 to 197)
28.0
(28 to 30)
FLT3 Mutation Negative Number Analyzed 1 participants 0 participants 2 participants 1 participants 1 participants 0 participants 0 participants
30.0
(30 to 30)
71.5
(71 to 72)
30.0
(30 to 30)
30.0
(30 to 30)
All Participants Number Analyzed 2 participants 0 participants 7 participants 27 participants 37 participants 3 participants 0 participants
43.5
(30 to 57)
57.0
(28 to 72)
30.0
(26 to 211)
31.0
(26 to 197)
28.0
(28 to 30)
31.Secondary Outcome
Title Time to Response (TTR)
Hide Description TTR was defined as the time from the first dose of study drug until the date of either first CRc or PR. TTR was evaluated for participants who achieved CRc or PR.
Time Frame From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
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Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CRc or PR were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 3 3 10 32 45 6 1
Median (Full Range)
Unit of Measure: days
FLT3 Mutation Positive Number Analyzed 2 participants 3 participants 8 participants 30 participants 43 participants 6 participants 1 participants
61.5
(29 to 94)
57.0
(31 to 64)
31.0
(28 to 59)
29.0
(26 to 211)
29.0
(26 to 197)
28.0
(26 to 61)
31.0
(31 to 31)
FLT3 Mutation Negative Number Analyzed 1 participants 0 participants 2 participants 2 participants 2 participants 0 participants 0 participants
30.0
(30 to 30)
71.5
(71 to 72)
29.5
(29 to 30)
29.5
(29 to 30)
All Participants Number Analyzed 3 participants 3 participants 10 participants 32 participants 45 participants 6 participants 1 participants
30.0
(29 to 94)
57.0
(31 to 64)
43.5
(28 to 72)
29.0
(26 to 211)
29.0
(26 to 197)
28.0
(26 to 61)
31.0
(31 to 31)
32.Secondary Outcome
Title Time to Best Response (TTBR)
Hide Description TTBR was defined as the time from the first dose of study drug until the first disease assessment date when participant achieved best response. TTBR was evaluated in participants who achieved best response of CR, CRp, CRi, or PR.
Time Frame From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CR, CRp, CRi, or PR were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 3 3 10 32 45 6 1
Median (Full Range)
Unit of Measure: days
FLT3 Mutation Positive Number Analyzed 2 participants 3 participants 8 participants 30 participants 43 participants 6 participants 1 participants
75.5
(57 to 94)
57.0
(31 to 64)
44.0
(28 to 315)
43.5
(26 to 364)
57.0
(26 to 245)
29.0
(26 to 61)
31.0
(31 to 31)
FLT3 Mutation Negative Number Analyzed 1 participants 0 participants 2 participants 2 participants 2 participants 0 participants 0 participants
30.0
(30 to 30)
71.5
(71 to 72)
29.5
(29 to 30)
29.5
(29 to 30)
All Participants Number Analyzed 3 participants 3 participants 10 participants 32 participants 45 participants 6 participants 1 participants
57.0
(30 to 94)
57.0
(31 to 64)
58.0
(28 to 315)
30.0
(26 to 364)
56.0
(26 to 245)
29.0
(26 to 61)
31.0
(31 to 31)
33.Secondary Outcome
Title Overall Survival (OS)
Hide Description The time from the date of first dose of study drug until the date of death from any cause. For a participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact. OS was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 16 16 24 70 100 20 3
Median (95% Confidence Interval)
Unit of Measure: days
FLT3 Mutation Positive Number Analyzed 14 participants 8 participants 12 participants 56 participants 89 participants 10 participants 2 participants
123.0
(17.0 to 267.0)
199.5
(56.0 to 905.0)
197.5
(61.0 to 329.0)
246.0
(190.0 to 309.0)
214.0
(126.0 to 264.0)
157.0
(20.0 to 218.0)
204.0
(51.0 to 357.0)
FLT3 Mutation Negative Number Analyzed 2 participants 8 participants 12 participants 14 participants 11 participants 10 participants 1 participants
NA [1] 
(227.0 to NA)
71.5
(5.0 to 180.0)
136.0
(14.0 to 314.0)
144.0
(83.0 to 195.0)
67.0
(21.0 to 336.0)
68.0
(8.0 to 249.0)
89.0 [1] 
(NA to NA)
All Participants Number Analyzed 16 participants 16 participants 24 participants 70 participants 100 participants 20 participants 3 participants
149.5
(31.0 to 267.0)
95.0
(55.0 to 195.0)
154.0
(74.0 to 299.0)
216.0
(161.0 to 285.0)
176.0
(124.0 to 253.0)
128.5
(36.0 to 199.0)
89.0
(51.0 to 357.0)
[1]
Data could not be calculated due to the low number of events.
34.Secondary Outcome
Title Event Free Survival (EFS)
Hide Description EFS was defined as the time from the date of first dose of study drug until the date of documented relapse, treatment failure or death from any cause, whichever occurred first. For a participant with none of these events, EFS was censored at the date of last relapse-free disease assessment. A participant without post-treatment disease assessment was censored at randomization date. Treatment failure included those participants who discontinued the treatment due to “progressive disease” or “lack of efficacy" without a previous response of CR, CRp, CRi or PR. Treatment failure date referred to the start of new anti-leukemia therapy or the last treatment evaluation date when new anti-leukemia therapy date was not available. For participants who were censored, last relapse-free disease assessment date referred to the participant’s last disease assessment date. EFS was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg
Hide Arm/Group Description:
Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed 16 16 24 70 100 20 3
Median (95% Confidence Interval)
Unit of Measure: days
FLT3 Mutation Positive Number Analyzed 14 participants 8 participants 12 participants 56 participants 89 participants 10 participants 2 participants
52.0
(14.0 to 88.0)
109.0
(29.0 to 357.0)
93.5
(61.0 to 127.0)
112.0
(92.0 to 143.0)
121.0
(92.0 to 155.0)
85.0
(11.0 to 157.0)
86.0
(51.0 to 121.0)
FLT3 Mutation Negative Number Analyzed 2 participants 8 participants 12 participants 14 participants 11 participants 10 participants 1 participants
58.0 [1] 
(NA to NA)
39.0
(5.0 to 67.0)
74.0
(12.0 to 131.0)
85.5
(37.0 to 126.0)
45.0
(21.0 to 113.0)
43.0
(8.0 to 83.0)
71.0 [1] 
(NA to NA)
All Participants Number Analyzed 16 participants 16 participants 24 participants 70 participants 100 participants 20 participants 3 participants
58.0
(19.0 to 88.0)
55.5
(38.0 to 92.0)
76.0
(61.0 to 119.0)
108.0
(90.0 to 126.0)
118.0
(88.0 to 140.0)
65.0
(20.0 to 100.0)
71.0
(51.0 to 121.0)
[1]
Data could not be calculated due to the low number of events.
35.Secondary Outcome
Title Leukemia Free Survival (LFS)
Hide Description LFS was defined as the time from the date of first CRc until the date of documented relapse or death for participants who achieved CRc. For a participant who was not known to have relapsed or died, LFS was censored on the date of last relapse-free disease assessment date. LFS was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS. Only participants who achieved CRc were included in the analysis.
Arm/Group Title Gilteritinib 20 mg Gilteritinib 40 mg Gilteritinib 80 mg Gilteritinib 120 mg Gilteritinib 200 mg Gilteritinib 300 mg Gilteritinib 450 mg